Molecular evolution is a critical research focus in the post-genome age of biology. With the current explosion of genome sequencing projects and the expansion of biomolecular structure databases, we finally have the opportunity to comprehensively appreciate and study the diversity and diversification of biological molecules. My research is focused on four areas within this field: 1) the origin and evolution of the approximately 1000 known basic types of protein structure, called folds; 2) the evolution of the function of sequence-specific DNA-binding proteins; 3) the evolution of proteins to avoid incorrect folding and aggregation, which can lead to many diseases, including Alzheimer's and prion disorders; 4) the evolution of protein toxins from nontoxic ancestor proteins. We approach these problems using a combination of computational studies (bioinformatics) with experimental structural biology (NMR and X-ray crystallography), biochemistry, and protein design
